title: MGMT Leu84Phe polymorphism contributes to cancer susceptibility: evidence from 44 case-control studies.
abstract: BACKGROUND
  O(6)-methylguanine-DNA methyltransferase is one of the few proteins to directly remove alkylating agents in the human DNA direct reversal repair pathway. A large number of case-control studies have been conducted to explore the association between MGMT Leu84Phe polymorphism and cancer risk. However, the results were not consistent.
  
  
  METHODS
  We carried out a meta-analysis of 44 case-control studies to clarify the association between the Leu84Phe polymorphism and cancer risk.
  
  
  RESULTS
  Overall, significant association of the T allele with cancer susceptibility was verified with meta-analysis under a recessive genetic model (P<0.001, OR=1.30, 95%CI 1.24-1.50) and TT versus CC comparison (P=0.001, OR=1.29, 95% CI 1.12-1.50). In subgroup analysis, a significant increased risk was found for lung cancer (TT versus CC, P=0.027, OR=1.67, 95% CI 1.06-2.63; recessive genetic model, P=0.32, OR=1.64, 95% CI 1.04-2.58), whereas risk of colorectal cancer was significantly low under a dominant genetic model (P=0.019, OR=0.84, 95% CI 0.72-0.97). Additionally, a significant association between TT genetic model and total cancer risk was found in the Caucasian population (TT versus CC, P=0.014, OR=1.29, 95% CI 1.05-1.59; recessive genetic model, P=0.009, OR=1.31, 95% CI 1.07-1.61), but not in the Asian population. An increased risk for lung cancer was also verified in the Caucasian population (TT versus CC, P=0.035, OR=1.62, 95% CI 1.04-2.53; recessive genetic model, P=0.048, OR=1.57, 95% CI 1.01-2.45).
  
  
  CONCLUSIONS
  These results suggest that MGMT Leu84Phe polymorphism might contribute to the susceptibility of certain cancers.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Renxia
authors.initials: R
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Cuicui
authors.initials: C
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Jia
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhang
authors.forename: Taufiq
authors.initials: T
authors.lastname: Salahuddin
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Juntian
authors.initials: J
authors.lastname: Lang
authors.forename: Xicheng
authors.initials: X
authors.lastname: Song
mesh_terms: D016022:Case-Control Studies; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D020125:Mutation, Missense / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D012044:Regression Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes